RT Journal Article SR Electronic T1 Phosphorylation of CREB at Serine 142 and 143 Is Essential for Visual Cortex Plasticity JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0217-21.2021 DO 10.1523/ENEURO.0217-21.2021 VO 8 IS 5 A1 Pulimood, Nisha S. A1 Contreras, Minerva A1 Pruitt, Molly E. A1 Tarasiewicz, Agnieszka A1 Medina, Alexandre E. YR 2021 UL http://www.eneuro.org/content/8/5/ENEURO.0217-21.2021.abstract AB The transcription factor cAMP response element-binding protein (CREB) is involved in a myriad of cellular functions in the central nervous system. For instance, the role of CREB via phosphorylation at the amino-acid residue Serine (Ser)133 in expressing plasticity-related genes and activity-dependent neuronal plasticity processes has been extensively demonstrated. However, much less is known about the role of CREB phosphorylation at Ser142 and Ser143. Here, we employed a viral vector containing a dominant negative form of CREB, with serine-to-alanine mutations at residue 142 and 143 to specifically block phosphorylation at both sites. We then transfected this vector into primary neurons in vitro or intracortically injected it into mice in vivo, to test whether these phosphorylation events were important for activity-dependent plasticity. We demonstrated by immunohistochemistry of cortical neuronal cultures that the expression of Arc, a known plasticity-related gene, requires triple phosphorylation of CREB at Ser133, Ser142, and Ser143. Moreover, we recorded visually-evoked field potentials in awake mice before and after a 7-d period of monocular deprivation (MD) to show that, in addition to CREB phosphorylation at Ser133, ocular dominance plasticity (ODP) in the visual cortex also requires CREB phosphorylation at Ser142/143. Our findings suggest that Ser142/143 phosphorylation is an additional post-translational modification of CREB that triggers the expression of specific target genes and activity-dependent neuronal plasticity processes.